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Genetic influences on antisocial behaviour, problem substance use and schizophrenia: evidence from quantitative genetic and molecular genetic studies
Published in John C. Gunn, Pamela J. Taylor, Forensic Psychiatry, 2014
Pamela J Taylor, Marianne BM van den Bree, Nigel Williams, Terrie E Moffitt
GABA is the primary inhibitory neurotransmitter in the central nervous system. GABAA receptor-mediated chloride currents into neurons are facilitated by a number of drugs, including ethanol, benzodiazepines and barbiturates. GABAA receptor genes α1 (GABRA1, chromosome 5), α2 (GABRA2, chromosome 4), α6 (GABRA6, chromosome 5) , β1 (GABBR1, chromosome 4), β2 (GABBR2, chromosome 9) and γ2 (GABRG2, chromosome 5) have all been associated with sensitivity to alcohol, alcoholism and/or antisocial alcoholism (Kreek et al., 2004; Ducci and Goldman, 2008; Gelernter and Kranzler, 2009; Ho et al., 2010).
The selective BDNF overexpression in neurons protects neuroglial networks against OGD and glutamate-induced excitotoxicity
Published in International Journal of Neuroscience, 2020
S. G. Gaidin, M. V. Turovskaya, M. S. Gavrish, A. A. Babaev, V. N. Mal’tseva, E. V. Blinova, E. A. Turovsky
The suppression of Ca2+ responses under GluTox and OGD in hippocampal neurons from (AAV)-Syn-BDNF-EGFP-transduced cultures can be mediated by the changes of expression or activity of excitatory glutamate receptors. According to the data of PCR analysis presented in Figure 7(A), expression of Grin2b gene encoding NR2B subunit of NMDA receptor decreased by 46% in cell cultures with neuronal BDNF overexpression, whereas the expression level of Grin2a gene encoding NR2A subunit did not change. The expression level of Gria1 gene encoding GluA1 subunit of AMPA receptor decreased by 23%. However, the expression level of Gria2 gene encoding GluA2 subunit increased by 37% (Figure 7(A)). The expression of Gabbr1 gene encoding β1 subunit of GABA(B) receptor increased by more than two times in cultures with neuronal BDNF overexpression. Nevertheless, the expression of Gabra1 gene encoding α1 subunit of GABA(A) receptor did not change (Figure 7(A)).
On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications
Published in Expert Review of Precision Medicine and Drug Development, 2020
Steven J. Nieto, Erica N. Grodin, Lara A. Ray
Alcohol modulates GABA activity directly at receptors and indirectly via stimulation of GABA release. The GABA system contains both ionotropic (GABAA) and metabotropic receptors (GABAB). Pharmacogenetic studies have focused on genes that encode subunits of the GABAA receptor, GABRA6 and GABRG2, as well as a gene that encodes a subunit of the GABAB receptor, GABBR1 (see Table 2). NTX and acamprosate-induced reductions in alcohol craving were dependent on GABRA6 genotype (T + 1519C) [49]. Acamprosate had greater efficacy on cue-induced craving in C homozygotes, while NTX had better efficacy in A carriers. This study also examined an SNP in GABRG2 (G + 3145A) that did not moderate NTX or acamprosate effects on cue-induced craving [49]. Variation in GABBR1 (rs29220) moderates treatment response to baclofen, a selective GABAB receptor agonist. Specifically, C homozygotes with AUD reported greater percentages of days abstinent, less drinking days, and an extended time to relapse compared to G carriers [75]. In sum, genetic variation in GABAergic signaling may be especially relevant to the subjective experience of alcohol [76] and may be useful in predicting treatment response, including clinical response to non-pharmacological treatments, such as Twelve Step Facilitation [77,78].
High-fat diet withdrawal modifies alcohol preference and transcription of dopaminergic and GABAergic receptors
Published in Journal of Neurogenetics, 2019
Luana Martins de Carvalho, Juliana Lauar Gonçalves, Agatha Sondertoft Braga Pedersen, Samara Damasceno, Renato Elias Moreira Júnior, Tatiani Uceli Maioli, Ana Maria Caetano de Faria, Ana Lúcia Brunialti Godard
Exon sequences were obtained from the Ensembl Genome Browser database (www.ensembl.org/; accessed 15 March 2015), and primers for quantitative real-time PCR (qPCR) were designed using Primer3 v.4.0.0 software, available online (http://primer3.ut.ee/; accessed 15 March 2015). The quality and specificity of the primer pairs were examined using NetPrimer software (www.premierbiosoft.com/netprimer/; accessed 15 March 2015) and Primer-BLAST software (www.ncbi.nlm.nih.gov/tools/primer-blast/; accessed 15 March 2015), respectively. All primers were positioned in inter-exon regions. Primers were synthesized by IDT – Integrated DNA Technologies (Síntese Biotecnologia, Belo Horizonte, Brazil) targeting the genes Drd1 and Drd2 (Dopamine receptor D1 and D2). The primer sequences are available in Table 1. Primers for the Gamma-Aminobutyric Acid Type B (GABAB) receptor subunit genes Gabbr1 and Gabbr2 were the same as defined in (Ribeiro et al., 2012). The sequence for references genes (Gapdh: glyceraldehyde 3-phosphate dehydrogenase and Ppia: peptidylprolyl isomerase A) was designed and tested as described previously in (Bibancos, Jardim, Aneas, & Chiavegatto, 2007).